Carcinogens interact with proteins in target organs undergoing chemical carcinogenesis. We are now studying a vitual loss of ability of liver during carcinogenesis to produce a principal carcinogen-protein complex. The change occurs under different experimental protocols with a consistency that is characteristic of an early marker of hepatocarcinogenesis. Further, the early marker is evident during liver carcinogenesis by at least two types of carcinogens. We will be examining other carcinogen-liver systems to determine how widespread this phenomenon is, and what are the nature and consequences of the loss of the ealy marker.